Tangier disease: a structural defect in apolipoprotein A-I (apoA-I Tangier).
Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins apo-A-I and apoA-II in patients with Tangier disease are approximately 1% and 7% of those in normal subjects, respectively. Previous studies have shown that the low plasma concentrations of apoA-I and apoA-II are due to increased fractional catabolism with a relatively normal apoA-I and apoA-II synthesis. Plasma apoA-I and apoA-II were isolated to electrophoretic homogeneity from delipidated plasma lipoproteins from a patient with Tangier disease. ApoA-I Tangier differed from apoA-I from control subjects in amino acid composition, electrophoretic mobility, apparent molecular weight on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and heterogeneity of isoforms on isoelectric focusing. ApoA-II Tangier, however, appeared to be identical to normal apoA-II in amino acid composition and in immunological as well as chemical properties. These results have been interpreted as indicating that apoA-I Tangier has a different covalent structure than does normal apoA-I, and apoA-II Tangier is identical to normal apoA-II. This structural change in apoA-I Tangier is associated with rapid catabolism of apoA-I Tangier-and apoA-II Tangier-containing plasma lipoproteins, and it leads to the deficiency in high density lipoproteins, abnormal chylomicron remnants, and the intracellular accumulation of cholesterol ester characteristic of Tangier disease.
D000596:Amino Acids / Q000032:analysis; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007009:Hypolipoproteinemias / Q000097:blood*; D005779:Immunodiffusion; D008075:Lipoproteins, HDL / Q000235:genetics*; D013631:Tangier Disease / Q000097:blood*
D000596:Amino Acids; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D008075:Lipoproteins, HDL